HYPOXIC CONTRACTION OF ISOLATED RABBIT MESENTERIC VEINS - CONTRIBUTION OF ENDOTHELIUM AND ATTENUATION BY VOLATILE ANESTHETICS

Background: Acute systemic hypoxia induces mesenteric venoconstriction in intact rabbits in part because of an increase in chemoreflex-media ted sympathetic efferent nerve activity, Inhaled anesthetics attenuate this reflex response, The direct effects of hypoxia on mesenteric vei ns are unknown, The purpose of the current study was to examine the ef fects of hypoxia on isolated rabbit mesenteric capacitance veins and t o determine the effects of halothane, isoflurane, and enflurane on the responses to hypoxia. Methods: Isometric tension was measured before, during, and after 10 min of hypoxia in the rings of either quiescent or norepinephrine contracted veins, with or without endothelium, Effec ts of various pharmacologic agents and volatile anesthetics on the res ponses to hypoxia were examined. Results: Hypoxia augmented contractio ns to norepinephrine and phenylephrine only in endothelium-intact vein s, The hypoxic response was inhibited by phentolamine (alpha-adrenocep tor antagonist) and abolished in the absence of extracellular Ca2+, Th ere were no effects of propranolol (beta-adrenoceptor antagonist), rya nodine (a sarcoplasmic reticulum Ca2+ depleter), indomethacin (cycloox ygenase inhibitor), or nordihydroguaiaretic acid (lipoxygenase inhibit or). L-NAME (an inhibitor of nitric oxide synthase) enhanced basal sen sitivity of veins to norepinephrine but had no effect on the response to hypoxia, Nicardipine (a blocker of voltage-gated calcium channels) depressed the hypoxic contraction by 86+/-5%, phosphoramidon (an inhib itor of endothelin-converting enzyme) by 82+/-8%, and BQ-123 (a specif ic endothelin-1 receptor antagonist) by 47+/-10%. Volatile anesthetics (1.0 MAC) inhibited responses to hypoxia in the absence as well as pr esence of L-NAME. Conclusions: These results suggest that in mesenteri c capacitance veins of rabbits an intrinsic vascular mechanism contrib utes to endothelium-dependent hypoxic augmentation of contraction to a lpha-adrenergic agonists that involve activation of endothelin-1, an e ndothelium-derived constricting factor. Inhibition of hypoxic contract ion by volatile anesthetics is not mediated by enothelium relaxing fac tor.